Mast cells are secretory cells associated with the connective tissue. They secrete over twenty preformed mediators, including histamine, in response to the binding of their surface sensitized IgE by ligand such as allergen. The mechanism of its secretion is not yet understood. The study of mast cell release may lead to a better understanding of the mechanism of neuronal secretion. Calcium is known to play a crucial role in the mechanism of secretion in general. There is strong evidence that calcium is also intimately involved in the mechanism of mast cell degranulation. We have localized a high calcium store in the granule using elemental X-ray microanalysis. Since intracellular free calcium is normally kept to a very low level (Less than 10 to the -6M), we have looked for the presence of calcium binding proteins. By using the coupled enzyme assay method of Chock and Huang, we have elucidated a calmodulin-like activity associated with the mast cell granules. Experiments are now being conducted to localize this calmodulin using an immunocolloidal gold ultrastructural technique. The possibility of the existence of different calmodulin binding proteins in mast cell is also of interest to us. Since we are already able to prepare calmodulin affinity column, we will employ this technique to identify these calmodulin binding proteins. We believe that the packaging of the granule content plays a crucial role in the regulation of the intragranular osmotic pressure in accordance to the chemo-osmotic model for secretion. We have been able to observe the ultrastructural organization of the granule by detergent extraction. A more systematic study to correlate the ultrastructural with biochemical changes will be undertaken.